In diverse eukaryotes, double-stranded RNA (dsRNA) triggers the destruction of mRNA sharing sequence with the double-strand (Hutvágner et al. (2002) Curr. Opin. Genet. Dev. 12:225-232; Hannon (2002) Nature 418:244-251). In animals and basal eukaryotes, this process is called RNA interference (RNAi) (Fire et al. (1998) Nature 391:806-811). There is now wide agreement that RNAi is initiated by the conversion of dsRNA into 21-23 nt fragments by the multi-domain RNase III enzyme, Dicer (Bernstein et al. (2001) Nature 409:363-366; Billy et al. (2001) Proc. Natl. Acad. Sci. USA 98:14428-14433; Grishok et al. (2001) Cell 106:23-34; Ketting et al. (2001) Genes Dev. 15:2654-2659; Knight et al. (2001) Science 293:2269-2271; and Martens et al. (2002) Cell 13:445-453). These short RNAs are known as small interfering RNAs (siRNAs), and they direct the degradation of target RNAs complementary to the siRNA sequence (Zamore et al. (2000) Cell 101:25-33; Elbashir et al. (2001) Nature 411:494-498; Elbashir et al. (2001) Genes Dev. 15:188-200; Elbashir et al. (2001) EMBO J. 20:6877-6888; Nykänen et al. (2001) Cell 107:309-321; and Elbashir et al. (2002) Clin. Pharmacol. 26:199-213). In addition to its role in initiating RNAi, Dicer also cleaves ˜70 nt precursor RNA stem-loop structures into single-stranded 21-23 nt RNAs known as microRNAs (miRNAs; Grishok et al. (supra); Hutvágner et al. (2001) Science 293:834-838; Ketting et al. (supra); and Reinhart et al. (2002) Genes Dev. 16:1616-1626). Like siRNAs, miRNAs bear 5′ monophosphate and 3′ hydroxyl groups, the signatures of RNase III cleavage products (Elbashir et al. (supra); Hutvágner et al. (supra). miRNAs are hypothesized to function in animals as translational repressors (Lee et al. (1993) Cell 75:843-854; Wightman et al. (1993) Cell 75:855-862; Ha et al. (1996) Genes Dev. 10:3041-3050; Moss et al. (1997) Cell 88:637-646; Olsen et al. (1999) Dev. Biol. 216:671-680; Reinhart et al. (2000) Nature 403:901-906; Zeng et al. (2002) Molecular Cell 9:1327-1333; and Seggerson et al. (2002) Dev. Biol. 243:215-225). The conversion of dsRNA into siRNAs requires additional protein co-factors that may recruit the dsRNA to Dicer or stabilize the siRNA products (Tabara et al. (1999) Cell 99:123-132; Grishok et al. (supra); Hammond et al. (2001) Science 293:1146-1150; and Tabara et al. (2002) Cell 109:861-871).